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The v-ATPase is a fundamental eukaryotic enzyme that is central to cellular homeostasis. Although its impact on key metabolic regulators such as TORC1 is well documented, our knowledge of mechanisms that regulate v-ATPase activity is limited. Here, we report that the Drosophila transcription<\/span> factor<\/span> Mitf<\/span> is a master regulator of this holoenzyme. Mitf<\/span> directly controls transcription<\/span> of all 15 v-ATPase components through M-box cis-sites and this coordinated regulation affects holoenzyme activity in vivo. In addition, through the v-ATPase, Mitf<\/span> promotes the activity of TORC1, which in turn negatively regulates Mitf<\/span>. We provide evidence that Mitf<\/span>, v-ATPase and TORC1 form a negative regulatory loop that maintains each of these important metabolic regulators in relative balance. Interestingly, direct regulation of v-ATPase genes by human MITF<\/span> also occurs in cells of the melanocytic lineage, showing mechanistic conservation in the regulation of the v-ATPase by MITF<\/span> family proteins in fly and mammals. Collectively, this evidence points to an ancient module comprising Mitf<\/span>, v-ATPase and TORC1 that serves as a dynamic modulator of metabolism for cellular homeostasis.<\/p>\n<\/div>\n<\/div>\n <\/p>","protected":false},"excerpt":{"rendered":" Im quite proud of helping with evolutionary and statistical analyses for a recent paper from Francesca Pignoni and colleagues. Zhang T, Zhou Q, Ogmundsdottir MH, M\u00f6ller K, Siddaway R, Larue L, Hsing M, Kong SW, Goding CR, Palsson A, Steingrimsson … Continue reading